Table Of ContentMolecular Pathology Library
Series Editor: Philip T. Cagle
Ashraf Khan · Ian O. Ellis
Andrew M. Hanby · Ediz F. Cosar
Emad A. Rakha · Dina Kandil Editors
Precision
Molecular
Pathology of
Breast Cancer
Molecular Pathology Library
Series editor
Philip T. Cagle, MD
More information about this series at http://www.springer.com/series/7723
Ashraf Khan, MD, FRCPath · Ian O. Ellis, MD,
FRCPath · Andrew M. Hanby, BM, FRCPath
Ediz F. Cosar, MD · Emad A. Rakha, MD,
FRCPath · Dina Kandil, MD
Editors
Precision Molecular
Pathology of Breast Cancer
1 3
Editors
Ashraf Khan, MD, FRCPath Ediz F. Cosar, MD
Department of Pathology Department of Pathology
University of Massachusetts Medical University of Massachusetts Medical
School School
UMassMemorial Medical Center UMassMemorial Medical Center
Worcester, MA Worcester, MA
USA USA
Ian O. Ellis, MD, FRCPath Emad A. Rakha, MD, FRCPath
Department of Histopathology Department of Histopathology
University of Nottingham University of Nottingham
Nottingham Nottingham
UK UK
Andrew M. Hanby, BM, FRCPath Dina Kandil, MD
Leeds Institute of Cancer and Pathology Department of Pathology
St. James University Hospital University of Massachusetts Medical
Leeds, West Yorkshire School
UK UMassMemorial Medical Center
Worcester, MA
USA
ISSN 1935-987X ISSN 1935-9888 (electronic)
Molecular Pathology Library
ISBN 978-1-4939-2885-9 ISBN 978-1-4939-2886-6 (eBook)
DOI 10.1007/978-1-4939-2886-6
Library of Congress Control Number: 2015942558
Springer New York Heidelberg Dordrecht London
© Springer Science+Business Media New York 2015
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Preface
The past decade has seen an immense growth in our understanding of the molecu-
lar basis of cancer, which has made a significant impact on how we manage cancer
in this era of personalized medicine. Breast cancer, which is the most common
malignancy in women in the western world, has been the vanguard in the applica-
tion of molecular pathology in its management. Advances in molecular pathology
have led to the development of new ancillary studies that are now standard clinical
practice for profiling of breast tumors permitting the tailoring of adjuvant treat-
ment. The investigations include diagnostic and predictive biomarkers determined
both by immunohistochemistry and more traditional molecular pathology tech-
niques such as FISH. At the advancing research front further potential new targets
of therapy within the molecular pathways underpinning current practice are being
revealed.
With the fast pace of growth in our knowledge, practicing physicians, includ-
ing pathologists, are increasingly expected to have a sound understanding of
both traditional morphology based interpretation and the molecular pathology of
breast cancer. Pathologists are consultants to their clinical colleagues for manag-
ing patients with breast cancer, and the role of molecular pathology has become
critical in this era of personalized medicine and multidisciplinary cancer care. It
is therefore important for pathologists to be familiar with advances in molecular
pathology of breast cancer, so they can provide a better, informed, opinion when
discussing cases with their clinical colleagues.
This book, which is part of the molecular pathology of cancer series, was put
together with the aim of combining histopathologic and cytomorphologic features
with changes at the molecular level, and how these latter alterations can play a
role in breast cancer management. The editors are experienced practicing diagnos-
tic breast pathologists who apply these molecular pathology techniques routinely
in their practice. With the exception of one chapter where we have invited breast
radiologist and medical physics experts to write on the molecular basis of breast
cancer imaging, all the authors in addition to diagnostic pathologists, include can-
cer biologists, who focus on the molecular biology of the breast cancer. The edi-
tors, who are also the senior author on each chapter, are internationally recognized
v
vi Preface
breast pathologists who bring their own valuable insights into the interface
between morphology and molecular pathology.
We are very grateful to all the contributors who have taken time out of their
busy schedules to write these chapters. We would also like to take this opportunity
to thank the series editor Dr. Philip Cagle for inviting us to write this book and the
editorial staff at Springer Publications for all their assistance in making this pro-
ject possible.
Ashraf Khan
Ian O. Ellis
Andrew M. Hanby
Ediz F. Cosar
Emad A. Rakha
Dina Kandil
Contents
1 Molecular Basis of Breast Cancer Imaging ..................... 1
Gopal R. Vijayaraghavan, Srinivasan Vedantham, Ashraf Khan
and Andrew Karellas
2 Familial Breast Cancer and Genetic Predisposition
in Breast Cancer ........................................... 15
Vighnesh Walavalkar, Ashraf Khan and Dina Kandil
3 Modelling the Molecular Pathology of Breast Cancer Initiation .... 39
Claire Nash, Andrew M. Hanby and Valerie Speirs
4 Molecular Pathology of Precancerous Lesions of the Breast ....... 51
Abhik Mukherjee, Ian O. Ellis and Emad A. Rakha
5 Breast Cancer Stem Cells: Role in Tumor Initiation, Progression,
and Targeted Therapy ....................................... 63
Sanjoy Samanta, Ashraf Khan and Arthur M. Mercurio
6 Molecular Pathology of Pre-Invasive Ductal Carcinoma .......... 79
Yuna Gong, Dina Kandil and Ashraf Khan
7 Molecular Pathology of Lobular Carcinoma .................... 95
Ali Sakhdari, Lloyd Hutchinson and Ediz F. Cosar
8 Molecular Pathology of Hormone Regulation in Breast Cancer:
Hormone Receptor Evaluation and Therapeutic Implications ...... 107
Emad A. Rakha
9 Molecular Pathology of HER Family of Oncogenes in Breast
Cancer: HER-2 Evaluation and Role in Targeted Therapy ........ 119
Ali Sakhdari, Lloyd Hutchinson and Ediz F. Cosar
vii
viii Contents
10 Molecular Classification of Breast Cancer ...................... 137
Mohammed A. Aleskandarany, Ian O. Ellis and Emad A. Rakha
11 Triple-Negative Breast Cancer: Subtypes with Clinical Implications ... 157
Dina Kandil and Ashraf Khan
12 Molecular-Based Diagnostic, Prognostic and Predictive
Tests in Breast Cancer ...................................... 177
Abir A. Muftah, Mohammed A. Aleskandarany, Ian O. Ellis
and Emad A. Rakha
13 Role of MicroRNAs in Breast Cancer .......................... 197
Jennifer L. Clark, Dina Kandil, Ediz F. Cosar and Ashraf Khan
14 Molecular Pathology of Fibroepithelial Neoplasms of the Breast ... 219
Michelle Yang, Dina Kandil and Ashraf Khan
15 Molecular Features of Mesenchymal Tumors of the Breast ........ 237
Marjan Mirzabeigi, Ashraf Khan and Dina Kandil
16 Molecular Pathology of Breast Cancer Metastasis ............... 271
Mohammed A. Aleskandarany, Ian O. Ellis and Emad A. Rakha
17 T he Molecular Pathology of Chemoresistance During
the Therapeutic Response in Breast Cancer ..................... 291
James L. Thorne, Andrew M. Hanby and Thomas A. Hughes
18 The Molecular Pathology of Male Breast Cancer ................ 309
Rebecca A. Millican-Slater, Valerie Speirs, Thomas A. Hughes
and Andrew M. Hanby
19 Specimens for Molecular Testing in Breast Cancer ............... 317
Ali Sakhdari, Lloyd Hutchinson and Ediz F. Cosar
Index ......................................................... 329
Contributors
Mohammed A. Aleskandarany Department of Histopathology, Division of Cancer
and Stem Cells, School of Medicine, The University of Nottingham and Nottingham
University Hospitals NHS Trust, Nottingham City Hospital, Nottingham, UK
Jennifer L. Clark Department of Pathology, University of Massachusetts Medical
School, UMassMemorial Medical Center, Three Bioetch, One Innovation Drive,
Worcester, MA, USA
Ediz F. Cosar Department of Pathology, University of Massachusetts Medical
School, UMassMemorial Medical Center, Worcester, MA, USA
Ian O. Ellis Division of Cancer and Stem Cells, Department of Histopathology,
School of Medicine, University of Nottingham and Nottingham University Hospitals
NHS Trust, Nottingham City Hospital, Nottingham, UK
Yuna Gong Department of Pathology, University of Massachusetts Medical
School, UMassMemorial Medical Center, Three Biotech, One Innovation Drive,
Worcester, MA, USA
Andrew M. Hanby St. James University Hospital/University of Leeds, Leeds
Institute of Cancer and Pathology (LICAP), Leeds, West Yorkshire, UK
Thomas A. Hughes Leeds Institute of Biologial and Clinical Sciences (LIBACS),
St. James University Hospital/University of Leeds, Beckett Street, Leeds, West
Yorkshire, UK
Lloyd Hutchinson Department of Pathology, University of Massachusetts Medical
School, UMassMemorial Medical Center, Worcester, MA, USA
Dina Kandil Department of Pathology, University of Massachusetts Medical School,
UMassMemorial Medical Center, Three Biotech, One Innovation Drive, Worcester,
MA, USA
Andrew Karellas Department of Radiology, University of Massachusetts Medical
School, Worcester, MA, USA
Ashraf Khan Department of Pathology, University of Massachusetts Medical
School, UMassMemorial Medical Center, Three Biotech, One Innovation Drive,
Worcester, MA, USA
ix
